In our opinions, IFN-α-based immunotherapies may benefit the following subpopulations of patients: (1) patients who have responded to intensive chemotherapy and stem cell transplantation, whose response may be deepened and prolonged by IFN-α-based immunotherapy; (2) patients with very early stage and/or indolent disease, limited tumor burden, and an intact immune response; (3) patients with robust anti-viral immunity, which can be reprogrammed to target cancer instead; and (4) patients with highly detectable proportions of circulating immune effector cells. This evidence concerns the gene IFNA2 and cancer.